Evidence obtained in this laboratory using mouse models suggests that lymphocytes, particularly thymus-derived lymphocytes, are important contributors to the inflammatory lung disease which can be caused by influenza virus infection. This project is aimed at identifying the immunologic mechanisms influencing the development of the inflammatory response to this infection. Virus inocula to be used are two derivatives of influenza A/Hong Kong virus which are equally infectious for mice but very different in their ability to cause pneumonia and death. Immunologically competent, athymic nude, irradiated and irradiated mice reconstituted with defined lymphocyte subpopulaions will be inoculated with the two virus derivatives. The models used will also include adoptive immunization of intact or compromised mice with lymph node and spleen cells, subpopulations of these cells, or other materials from previously vaccinated or inoculated donor mice, and intranasal challenge of the recipients with influenza virus. Control studies will utilize cells or other materials from unexposed donor mice and from mice vaccinated with an influenza serotype differing from the challenge virus. Indices of infection and gross and microscopic quantitation of inflammation will be measured sequentially after inoculation and correlated with the number, identity and functional competency of immunocytes from lung, bronchoalveolar lavage, thymus, spleen and peripheral nodes. Functional assays will include those for blastogenic response, lymphocyte mediated cytotoxicity, and interferon release. Virological studies will be done and correlated with both disease and immune parameters. The results of these studies and the contrast between the effects of infection with the 2 different influenza virus derivatives should and in defining the interactions and importance of immunopathologic processes in virus-induced inflammation of the lung.